ANGIOTENSIN-II-INDUCED HYPERTENSION INCREASES HEME OXYGENASE-1 EXPRESSION IN RAT AORTA

Background We investigated the in vivo effects of angiotensin (Ang) II -induced hypertension on heme oxygenase (HO) mRNA and protein expressi on, activity, and localization in rat aortas. Methods and Results Infu sion of Ang II (0.7 mg.kg(-l).d(-1)) increased HO-1 mRNA levels to 169 +/- 31%, 251 +/- 47%, 339 +/- 26%, and 370 +/- 74% of the control lev el at 1, 3, 5, and 7 days after operation, respectively. The HO-1 prot ein level at 7 days was markedly upregulated, as was HO activity. Trea tment with either losartan (25 mg.kg(-1).d(-1)) or hydralazine (15 mg. kg(-1).d(-1)), both of which prevented the Ang II-induced hypertensio n, blocked HO-1 mRNA upregulation. Norepinephrine infusion (2.8 mg.kg( -1).d(-1)) produced a degree of hypertension and degree of HO-1 mRNA u pregulation similar to those of Ang II infusion, which was again block ed by treatment with hydralazine (382 +/- 18% and 150 +/- 30% of the c ontrol level, respectively). Immunohistochemical analysis demonstrated that HO-1 is expressed in medial smooth muscle and adventitial cells in normotensive rat aortas, and this is markedly increased in adventit ial and endothelial cells in Ang II-induced hypertensive rat aortas. I n contrast, HO-2 protein expression was not changed in hypertensive ra t aortas. Conclusions These findings indicate that HO-1 is upregulated in hypertensive rat aortas, apparently by mechanisms unique to Ang II and by hemodynamic stress.